Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE) is a rare autosomal recessive disease with prominent gastrointestinal initial manifestation. We hereby report a novel TYMP mutation of MNGIE inherited by maternal isodisomy, who presented with debilitating symptoms of peripheral neuropathy due to concurrent Charcot-Marie-Tooth disease (CMT).

Proband is a 23-year-old lady from Dusun descendant, an indigenous tribe in Borneo, Malaysia. She presented with one year of lower limb weakness requiring walking aid, ptosis and complex external ophthalmoplegia. Initial cerebrospinal fluid and nerve conduction study (NCS) was suggestive of Chronic Inflammatory Demyelinating Polyneuropathy. However, she did not respond to intravenous immunoglobulin treatment. There were other confounding features such as diabetes mellitus, hyperlactatemia, hepatomegaly, and asymptomatic leukoencephalopathy from MRI scan. 

Further family history discovered her father and sister are affected with ptosis and distal weakness. Family pedigree was suspicious of an autosomal dominant inheritance. However Whole Exome Sequencing of proband revealed 2 mutations. One being heterozygous duplication at PMP22 suggestive of CMT1a, another being a novel homozygous mutation c1187C>T at TYMP. Subsequent urine quantification confirmed MNGIE with raised thymidine and deoxy uridine. 

The proband’s mother was heterozygous for the novel TYMP mutation whereas her symptomatic father was negative for TYMP mutation. Consultation with geneticist suggest that proband inherited the homozygous TYMP mutation via maternal isodisomy. Her father (TYMP negative) and sister (TYMP heterozygous) are likely to be suffering from CMT1a with their slow nerve conduction velocities within the typical range of 15-35m/s.

Hickum’s dictum prevails in this case with both diseases contributing to the severity and predominance of the proband’s neurological symptoms. Emphasis on confounding clinical features shall not be taken lightly to not overlook a concurrent disease that is potentially treatable.