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Ethylmalonic encephalopathy (EE) is a rare, severe, autosomal recessive condition caused by pathogenic variants in ETHE1 leading to progressive encephalopathy, hypotonia evolving to dystonia, petechiae, orthostatic acrocyanosis, diarrhea, and elevated ethylmalonic acid in urine. In this case report, we describe a patient with only mild speech and gross motor delays, subtle biochemical abnormalities, and normal brain imaging found to be homozygous for a pathogenic ETHE1 variant (c.586G>A) via whole exome sequencing. This case highlights the clinical heterogeneity of ETHE1 mutations and the utility of whole-exome sequencing in diagnosing mild cases of EE.

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Glycogen storage disease type 1a (GSD1a) is an inborn error of glucose metabolism characterized by fasting hypoglycemia, hepatomegaly, and growth failure. Late complications include nephropathy and hepatic adenomas. We conducted a retrospective observational study on a cohort of Amish patients with GSD1a. A total of 15 patients cared for at a single center, with a median age of 9.9 years (range 0.25-24 years) were included. All patients shared the same founder variant in GCPC c.1039 C > T. The phenotype of this cohort demonstrated good metabolic control with median cohort triglyceride level slightly above normal, no need for continuous overnight feeds, and a higher quality of life compared to a previous GSD cohort. The most frequent complications were oral aversion, gross motor delay, and renal hyperfiltration. We discuss our unique care delivery at a single center that cares for Amish patients with inherited disorders.

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Infants with critical congenital heart defects (CCHDs) are at increased risk for neurodevelopmental delays. The early identification of motor delays is clinically relevant to prevent or reduce long-term consequences. The current study aims to describe the motor-developmental pathways of infants with a CCHD. Motor development was assessed in 215 infants and toddlers using the Dutch version of the Bayley-III. At 3 months (n = 165), 9 months (n = 188), and 18 months (n = 171) the motor composite scores were 97, 98, and 104, respectively. A motor composite score of ≤-2 SD was only seen in 2.4%, 0%, and 2.3%, respectively, with gross motor deficits being observed more often than fine motor deficits (12% vs. 0% at 18 months). Over 90% of infants who scored average at 9 months still did so at 18 months. The majority of infants with below-average gross motor scores (≤-1) at 9 months still had a below-average or delayed motor score (≤-2 SD) at 18 months. Abnormal gross motor scores (≤-2 SD) increased with age. Infants with single-ventricle physiology performed significantly (p ≤ 0.05) worse on both fine and gross motor skills at 9 and 18 months compared to infants with other CCHDs.

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BACKGROUND: Sarcopenia is defined as reduced skeletal muscle mass (SMM) or myopenia and altered muscle function and physical performance. It is unknown whether myopenia in children with end-stage liver disease (ESLD) adversely impacts clinical outcomes. We hypothesized that myopenia was prevalent in children with ESLD and related to suboptimal nutrition intake contributing to gross motor and growth delay, increased hospitalization, and medical complications. METHODS: This retrospective study evaluated abdominal imaging (computed tomography/magnetic resonance imaging) for SMM (total, psoas, paraspinal, abdominal wall muscle; cm2 /height2 ) and adipose tissue (total, visceral, subcutaneous adipose tissue [SAT], ) determinations at the third and fourth lumbar vertebrates during liver transplantation (LTx) assessment. ESLD children (n = 30) were age- and gender-matched to healthy controls (n = 24). Myopenia was defined as SMM index z score <-2 and low SAT was defined as SAT index z-score <-1.5. Anthropometric, biochemical, and clinical data (hospitalization, complications, growth, neurodevelopment, energy/protein intake) were collected at LTx assessment, LTx, and post LTx (first hospitalization, 6 months, 12 months). RESULTS: Four distinct body composition phenotypes in children with ESLD were found: (1) myopenia with low SAT (17%;5 of 30), (2) myopenia (3%;1 of 30), (3) low SAT (20%;6 of 30), (4) normal muscle mass and SAT (60%;18 of 30). Myopenia with low SAT was prevalent in older (>2 years), male children and was associated with gross motor delay, reduced energy intake, and increased hospitalization and infections (total/viral/fungal). CONCLUSIONS: Myopenia, accompanied by low SAT in children with ESLD, is associated with adverse clinical outcomes. Rehabilitation strategies aimed at combating myopenia in children are important.

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AIM: Vitamin D deficiency in early pregnancy may cause the disruption of fetal brain development and neurodevelopmental function. This study aimed to explore the extent of neurodevelopment disruption could be associated with maternal vitamin D deficiency. METHODS: A cohort study was conducted in Sukabumi and Waled, West Java, Indonesia, beginning in July 2016. Maternal serum 25(OH)-vitamin D was measured between 10 and 14 weeks of gestational age. Child development was measured using the Ages and Stages Questionnaire-3 (ASQ-3) at age 3, 6 and 12 months. RESULTS: A total of 141 mother-infant pairs participated. One pair was excluded due to anencephaly of the infant. Vitamin D deficiency was found in 27 (19%) mothers, but delays occurred in gross motor function among 104 (76.1%) infants and in problem-solving functions among 61 (43.7%) infants at 3 months old. In general, the mean ASQ score at ages 3 and 6 months were lower among infants whose mothers had a vitamin D deficiency. The mean ASQ score for gross motor function at age 3 months was found to be significantly lower among these infants (31.5 vs. 37.9; P = 0.02), with increased risk for delayed motor function at age 3 months (relative risk (95% confidence interval) = 1.22 (1.09-1.49); P = 0.03). CONCLUSION: Neurodevelopmental function disruptions among infants whose mothers had vitamin D deficiency during pregnancy were reflected in lower ASQ scores, in which gross motor function was significantly impaired at 3 months of age.

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Interstitial and terminal 6q25 deletions are associated with developmental delays, hypotonia, eye pathologies, craniofacial dysmorphologies, and structural brain anomalies. In most cases, speech and language deficits are not described in detail. We report on a case (Patient 1, age 7 years) with a de novo 6q25.3-qter deletion, 11.1 Mb long and encompassing 108 genes, and a case (Patient 2, age 5 years) with an inherited interstitial 6q25.3 deletion, located within Patient 1's deletion region and 403 kb long, the smallest 6q25 deletion reported to date. Both children have hypotonia, motor speech disorders, and expressive language delays. Patient 1's speech was characterized by childhood apraxia of speech (CAS) and dysarthria. Other findings include developmental delay, ataxic cerebral palsy, optic nerve dysplagia, and atypical brain morphologies regarding the corpus callosum and gyration patterns, a clinical profile that closely matches a previously reported case with a nearly identical deletion. Patient 2 had speech characterized by CAS and typical nonverbal processing abilities. His father, a carrier, had typical speech and language but showed difficulties with complex motor speech and hand motor tasks, similar to other adults with residual signs of CAS. The small deletion in this family contains the IGF2R-AIRN-SLC22A2-SLC22A3 gene cluster, which is associated with imprinting and maternal-specific expression of Igf2R, Slc22a2, and Slc22a3 in mice, whereas imprinting in humans is a polymorphic trait. The shared phenotypes in the two patients might be associated with the deletion of the gene cluster.

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AIMS: Watch Me Move (WMM) is a 6-week parent education program for caregivers of children with gross-motor delays. The aims are to improve parent-child interaction in a gross-motor context, increase parents' knowledge of behavioral cues and gross-motor development, and decrease perceived parental stress. METHODS: Forty mothers of children, 6 months to 3 years of age, with a gross-motor delay participated in a randomized control trial comparing parents who received the WMM program plus standard of care physiotherapy (n = 24) with parents whose children received standard of care physiotherapy (n = 16). RESULTS: Mothers who received the WMM program had significantly higher change scores on two subscales of the Nursing Child Assessment Teaching Scale (NCATS; i.e., cognitive growth fostering, and responsiveness to caregiver) and on the Parent Knowledge Questionnaire assessing knowledge of behavioral cues and gross-motor development. There were no significant group differences on the other four NCATS subscales (i.e., sensitivity to cues, response to child's distress, social emotional growth fostering, and clarity of cues) or the Parenting Stress Index. CONCLUSIONS: The addition of WMM to traditional physiotherapy improved aspects of mothers' ability to interact with their children and their knowledge of behavioral cues and gross-motor development.

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