Clinical Guidance
Infants with untreated TRMU deficiency, a mitochondrial disorder, typically become symptomatic between ages two and four months with transient acute liver dysfunction (including elevated transaminases, abnormal synthetic functions, and/or hepatomegaly), metabolic derangements (severe persistent lactic acidosis, hypoglycemia, hyperammonemia), and poor weight gain. With proper supportive treatment (but not disease-targeted therapy), abnormal liver findings (including coagulopathy) improve or normalize, as do metabolic derangements. Lactic acidemia typically improves, but typically does not fully normalize. Neurologic dysfunction may persist or evolve over time . Early targeted therapy (i.e., L-cysteine and N-acetylcysteine [NAC] supplementation) may significantly alter the disease course based on the limited experience to date with two unrelated at-risk sibs who were diagnosed prenatally or shortly after birth. These two children, who were treated presymptomatically, had a milder disease course with less severe acidosis and liver dysfunction and fewer hospitalizations than their affected sibs . To date, 62 individuals (60 probands and two at-risk sibs) have been identified with biallelic pathogenic variants in TRMU [, , , , , , , , , ]. Untreated Symptomatic Children at the Time of Diagnosis The following is a description of the features associated with TRMU deficiency in 60 untreated symptomatic children at the time of diagnosis . Table 3. TRMU Deficiency: Frequency of Select Features in Untreated Symptomatic Children at the Time of Diagnosis
