Early onset cardiomyopathy: The most common and most severe phenotype observed in MTP deficiency is the early onset cardiomyopathy and often leads to infantile death. This cardiomyopathy usually presents with a rapidly progressing neonatal cardiomyopathy. The median age at first presentation in clinic for MTP deficiency patients was reported at 3 months of age and nearly half of the cases were reported within 4 weeks of age with a rapid progression often fatal within 8 weeks after the first presentation.
The intermediate phenotype is characterized by hypoketotic/hypoglycemia. The clinical presentation of MTP deficiency patients presenting with the hepatic phenotype is poorly reported in the literature. Several accounts of hepatic phenotype have reported developmental delay with liver dysfunction accompanied by episodes of lactic acidemia, comas and convulsions. Additionally, other accounts of the hepatic phenotype have reported deaths from viral infections. MTP deficiency can affect the liver’s ability to supply energy to the vital organs in fasted states through dysfunction in gluconeogenesis and ketogenesis leading to a hepatic phenotype associated with delayed development, fragile immunity and hepatic encephalopathy. Furthermore, the heterogeneity of the clinical presentation of this phenotype may contribute to the poor diagnosis observed in the literature.
Mild (late-onset) phenotype is characterized by myopathy and/or neuropathy: clinical presentation of the rhabdomyolysis is quite diverse, and diagnosis may be delayed. Nevertheless, common clinical features should alert the clinicians; HADHB-patients usually present with one of these three consistent symptoms: muscular pain, weakness and reddish-brown urine. Although the phenotypic implications are heavily heterogeneous for HADHA and HADHB mutations, the largest study on the topic has found that over 50% of HADHB mutations, predominantly missense, are accompanied by peripheral neuropathy. Diagnosis is made from a combination of family history, genomic testing, normal or slightly abnormal nerve conduction velocity (30-45 m/s), EMG evidence of axonal neuropathy such as positive waves, polyphasic potentials and fibrillations as well as greatly reduced compound muscle action potential (CMAP) amplitudes.
HADHB