PEMPix is the American Academy of Pediatrics Section on Emergency Medicine’s annual visual diagnosis competition. This year, in addition to the 10 finalists Maneesha Agarwal will be presenting at the National Conference and Exhibition we will be sharing four cases online in advance of the conference. This is the fourth of the four cases.

This case was submitted by…

A previously healthy 19-month-old male presented with lethargy and abdominal distention from an urgent care. His Mother noted that this morning he was difficult to arouse, unwilling to wake up, and his abdomen was more distended than usual. There is no recent history of vomiting, diarrhea, cough, cold, congestion, fevers, trauma, or any known ingestion.

Physical exam

Vital Signs: Temperature: 37.9 °C, HR: 193, BP: 141/90, RR: 27, SpO2: 97% on RA

HENT: Normocephalic and atraumatic

Eyes: Pupils are equal, round and reactive. Normal tracking

Cardiovascular: Tachycardia. Regular rhythm

Pulmonary: Normal effort. Clear in bilateral lung fields

Abdominal: Distention. No tenderness. No palpable mass

Genitourinary: Penis and testes normal

Skin: Warm and dry. Capillary refill less than 2 seconds

Lymphadenopathy: No cervical lymphadenopathy

Neurological: Moving all extremities. Irritable and sleepy

Relevant Labs

Hgb 9.9 mg/dL

Hct 30.7%

Platelets 134 × 109/L

Alk phos 470 U/L

AST 84 U/L

ALT 40 U/L

VBG pH 7.320, pCO2 81, HCO2 22

Urine Drug Screen positive for cannabinoids

The patient had chest x-ray without any notable pathology. A CT scan of his head was obtained due to his lethargy, and was negative for any acute pathology. His abdominal x-ray is pictured here.

Based on his x-ray and abnormal labs, a CT of his abdomen and pelvis was also obtained with one relevant image shown here:

A. Hepatic cancer
B. Hepatic hemangioma
C. Cannabinoid poisoning
D. Entamoeba histolytica infection
E. Tyrosinemia

E. Tyrosinemia

The patient’s CT scan revealed liver replaced and distorted by innumerable, variably-enhancing nodules, as well as nephromegaly. He was ultimately admitted to the general pediatric service for further management. Initial labs revealed an AFP that was elevated at 7,000 raising concern for malignancy, so a liver biopsy was performed to exclude malignancy. However this biopsy revealed evidence of fibrosis and no concern for malignancy. Additional labs ordered per the consultant’s recommendations were notable for elevated PT/PTT, AFP, plasma tyrosine, and urine succinylacetone consistent with a diagnosis of tyrosinemia.

The patient was ultimately diagnosed with tyrosinemia type 1, an autosomal recessive disorder of amino acid metabolism. In this form of tyrosinemia, a deficiency in the last enzyme responsible for tyrosine metabolism (fumarylacetoacetate hydrolase deficiency) is deficient leading to the build up of toxic metabolites (fumarylacetoacetate). Infants may present with acute liver impacts in the first few months of life; subacute with less overt liver impacts, or, like this patient, with chronic impacts after six months with less significant symptoms. In the chronic form of the disease, eventual accrual of toxins results in failure to thrive, liver disease, and renal failure. They may also have a porphyria-like presentation. Mixed micronodular and macronodular cirrhosis is common in these patients may begin to develop in utero. If not diagnosed, infants with tyrosinemia can die of liver failure within a few years of birth. They are also at high risk of hepatocellular carcinoma.

Tyrosinemia type 1 is part of the newborn screen in the majority of states, however the disease can be missed if screening uses tyrosine levels as the biomarker instead of more sensitive succinylacetone levels. Management includes diets avoiding phenylalanine and tyrosine and the use of nitisinone, which works on the tyrosine metabolism pathway before toxic metabolites are formed. Liver transplantation, which is curative, may be required for patients who do adequately respond to the aforementioned interventions or those who develop liver cancer; transplantation is ultimately curative.

Note: The patient’s initial lethargy was felt to be due to ingestion of a THC gummy rather than his tyrosinemia.

References

Disorders of tyrosine metabolism. UpToDate.

Rashad MM, Nassar C. Tyrosinemia Typel: A case report. Sudan J Paediatr. 2011;11(1):64-7. PMID: 27493308; PMCID: PMC4949785.

Sniderman King L, Trahms C, Scott CR. Tyrosinemia Type I. 2006 Jul 24 [Updated 2017 May 25]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1515/

Kvittingen EA. Hereditary tyrosinemia type I–an overview. Scand J Clin Lab Invest Suppl. 1986;184:27-34. PMID: 3296130.

Barroso F, Correia J, Bandeira A, Carmona C, Vilarinho L, Almeida M, Rocha JC, Martins E. TYROSINEMIA TYPE III: A CASE REPORT OF SIBLINGS AND LITERATURE REVIEW. Rev Paul Pediatr. 2020 Jun 5;38:e2018158. doi: 10.1590/1984-0462/2020/38/2018158. PMID: 32520295; PMCID: PMC7274528.

https://newbornscreening.hrsa.gov/conditions/tyrosinemia-type-i

https://rarediseases.org/rare-diseases/tyrosinemia-type-1/